Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome and celiac disease in a 13-year-old girl: further evidence for autoimmunity?

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare and potentially lethal disorder. The etiology is unclear but paraneoplastic syndrome and autoimmunity secondary to neural crest tumors have been considered, even in patients without any detectable tumor due to their tendency for spontaneous remission. We are presenting a 13-year-old girl with ROHHAD syndrome and celiac disease, which may suggest further evidence for immune-mediated etiology in the pathogenesis of ROHHAD syndrome.

Differences in parental involvement in the care of children and adolescents with type 1 diabetes mellitus on multiple daily insulin injections versus continuous subcutaneous insulin infusion.

BACKGROUND: Assessing the degree of involvement of caregivers for children with type 1 diabetes mellitus (T1DM) in their diabetes care, differences in the degree of involvement based on the method of insulin administration (multiple daily injections: MDI/continuous subcutaneous insulin infusion: CSII), and its effect on glycemic control. METHODS: This was a cross-sectional study with T1DM patients, ages 6-13 years using a six question survey derived from the Diabetes Family Responsibility Questionnaire (DFRQ). All caregivers (n=140) and participants between ages 11 and 13 (n=60) completed the survey. RESULTS: Significant differences between MDI and CSII caregiver responses were found for responsibility for giving insulin boluses, as well as for rotation of infusion/injection sites (p<0.001 and p=0.03, respectively). A sub-analysis of caregiver responses for caregiver versus child responsibility for giving infusion boluses (excluding shared responsibility) showed that 36% of children in the CSII group had primary responsibility for giving insulin boluses, compared to 17% in the MDI group (p<0.001). The median agreement for all questions combined between participants and caregivers for ages 11-13 (n=60 pairs) was "poor" (κ=0.18). No significant effect of parental involvement on last 2-year average HbA1C was found for CSII or MDI groups (p>0.20). CONCLUSIONS: Caregiver reported diabetes care responsibility (mostly parent, mostly child, shared between parent and child) varies for certain aspects of diabetes related care for children ages 6-13, depending upon the mode of insulin administration. Based on the reported degree of parental collaboration, HbA1C did not differ significantly. However, long-term effects are yet to be determined in longitudinal studies.

Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study.

BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition with variable clinical pictures and spectrum of findings. OBJECTIVE: To analyze the spectrum of findings, frequency and age of onset of hypothalamic-pituitary dysfunctions in children with SOD. METHOD: A retrospective electronic medical record (EMR) chart review was done for patients with SOD seen in a tertiary care center's pediatric endocrinology clinic between January 1, 2012, and March 31, 2014. The diagnostic criteria for SOD included presence of ≥ 2 of the following: (i) optic nerve hypoplasia, (ii) agenesis/hypoplasia of septum pellucidum and/or corpus callosum and (iii) hypothalamic-pituitary dysfunction. RESULTS: Eighty patients fitting the diagnostic criteria of SOD were included in this study. The majority of patients (96%) had optic nerve hypoplasia on magnetic resonance imaging and were diagnosed due to visual issues including nystagmus (36%) or strabismus (13.8%). Hypothalamic-pituitary dysfunction was most common (51%) when optic nerve hypoplasia was present with (36%) or without (15%) dysgenesis of septum pellucidum and/or corpus callosum compared to dysgenesis of septum pellucidum and/or corpus callosum alone (4%). Hypothalamic-pituitary dysfunction was noted in 55% of patients, and most (86%) were diagnosed ≤ 2 years of age. Central hypothyroidism and growth hormone deficiency were most common followed by secondary/tertiary adrenal insufficiency and diabetes insipidus. CONCLUSIONS: The risk of hypothalamic-pituitary dysfunction in SOD is highest ≤ 2 years of age and when both optic nerve hypoplasia and dysgenesis of septum pellucidum/corpus callosum are present, suggesting a need for more frequent follow-up and screening tests for hypothalamic-pituitary dysfunction in these patients.

Fear of needles in children with type 1 diabetes mellitus on multiple daily injections and continuous subcutaneous insulin infusion.

OBJECTIVE: To assess the prevalence of fear of needles and its effect on glycemic control in children with type 1 diabetes mellitus (T1DM) on multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). METHODS: Patients aged 6 to 17 years with T1DM on MDI or CSII (n = 150) were enrolled. All caregivers and patients aged ≥11 years completed a "Diabetes Fear of Injecting and Self-testing Questionnaire" (D-FISQ). Needle phobia was defined as a score ≥6 for fear of self-testing (FST), fear of injections (FI), and fear of infusion-site changes (FISC). RESULTS: Positive FST scores were noted in 10.0% and positive FI or FISC scores in 32.7% (caregivers' responses). Patients aged 6 to 10 years on CSII had greater fear (FISC) than those on MDI (FI) (P = .010). FST was inversely related to the number of daily blood sugar checks (P = .003). Patients with positive scores for FI/FISC or FST had significantly higher glycated hemoglobin (HbA1c) levels than those without. An inverse association was noted between positive FI/FISC scores and age of the patient (P = .029). Based on patient responses, FST severity was directly related to the age of the patient (P = .013). CONCLUSION: Needle phobia is common in children with T1DM. Although FI/FISC are more common in younger children, especially in those on CSII, FST is more often encountered in older patients. Patients with a more intense fear of needles have higher HbA1c levels and less frequent blood sugar monitoring. Identifying these patients may help improve glycemic control.

Real-time continuous glucose monitoring among participants in the T1D Exchange clinic registry.

OBJECTIVE: To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS: Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS: Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS: CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

Atypical neurologic presentations of new onset type 1 diabetes mellitus in pediatric age group: a report of five unusual cases and review of the literature.

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in childhood and is caused by insulin deficiency resulting from the autoimmune destruction of insulin producing beta cells of the pancreas. Most children in the US with new onset T1DM present with the classic signs and symptoms of hyperglycemia and 30% with diabetic ketoacidosis (DKA). Neurologic manifestations are relatively rare and mostly include lethargy, decreased level of consciousness, and coma as a result of DKA. In this article, five cases of new onset T1DM with exceedingly rare or unreported neurologic manifestations in the pediatric age group are presented, along with a review of the literature.

Comparison of the expectations of caregivers and children with type 1 diabetes mellitus for independence in diabetes care-related tasks.

OBJECTIVE: Children who are given unsupervised responsibility for their diabetes care prior to developmental and/or emotional readiness may have poorer glycemic control. The purpose of this study was to assess the age-related expectations of children and caregivers for independence in diabetes care-related tasks. METHODS: A total of 150 participants with type 1 diabetes mellitus (T1DM) receiving multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) were enrolled in this study. All caregivers and participants older than 10 years of age completed questionnaires evaluating the expected age of independence for different diabetes care-related tasks. RESULTS: The participants expected independence with no direct supervision in most diabetes care-related tasks at a younger age than their caregivers (P<.05). The difference was more prominent for those on CSII compared to MDI (P<.01). There was a positive correlation between the age when caregivers expect independence for most of the diabetes-related tasks and the age at diagnosis, regardless of the use of MDI or CSII (P<.01). CONCLUSION: Children with T1DM expect to assume independence at a younger age than their caregivers do. The younger the children are at diagnosis, the younger they are expected by their caregivers to be independent, especially those on CSII.

Basal and bolus insulin requirements in children, adolescents, and young adults with type 1 diabetes mellitus on continuous subcutaneous insulin infusion (CSII): effects of age and puberty.

OBJECTIVE: Guidelines for insulin dosing, including the insulin to carbohydrate ratio (I/C), insulin sensitivity factor (ISF), and basal/bolus ratio guidelines, have been well established for adults with type 1 diabetes mellitus (T1DM). However, clinical experience suggests that these guidelines are not appropriate for children. The purpose of this study was to determine the continuous subcutaneous insulin infusion (CSII) settings in children with T1DM at different ages and stages of puberty. METHODS: A total of 154 patients data between the ages of 3 and 21 years with well-controlled T1DM according to American Diabetes Association guidelines were reviewed. Only patients on CSII who were not in the honeymoon period were included. RESULTS: Patients were divided into 8 groups according to age, gender, and/or pubertal stage. Insulin requirements increased with puberty in both sexes (0.69, 0.97, and 0.90 U/kg/day in children <7 years of age, midpubertal girls, and late-pubertal boys, respectively). Basal insulin requirement was lowest in the youngest group (34%; P<.01). The youngest group had the lowest I/C prediction factor (PF) (mean, 315.7 ± 79.4; P<.01 with all groups), and the ISF-PF was higher than that of the oldest group (mean, 2,588.3 ± 1,101.8; P<.01). CONCLUSION: CSII dose calculations vary with age and pubertal status in children with T1DM. These differences must be considered when calculating CSII dosing, especially for younger children.

Comparison of the effect of insulin glulisine to insulin aspart on breakfast postprandial blood glucose levels in children with type 1 diabetes mellitus on multiple daily injections.

OBJECTIVE: Rapid-acting insulins, including insulin aspart (NovoLog) and lispro (Humalog), do not seem to effectively control postprandial glycemic excursions in children with type 1 diabetes mellitus (T1DM). The objective of this study was to determine if insulin glulisine (Apidra), another rapid-acting insulin analog, would be superior in controlling postprandial hyperglycemia in children with T1DM. METHODS: Thirteen prepubertal children ages 4 to 11 years completed this study. Inclusion criteria included T1DM ≥6 months, glycosylated hemoglobin (HbA1C) 6.9 to 10%, blood glucose (BG) levels in adequate control for 1 week prior to study start, multiple daily injections (MDI) with insulin glargine or determir once daily and aspart or lispro premeal. If fasting BG was 70 to 180 mg/dL, subjects received insulin glulisine alternating with aspart prior to a prescribed breakfast with a fixed amount of carbohydrate (45, 60, or 75 g) for 20 days. Postprandial BG values were obtained at 2 and 4 hours. RESULTS: Mean baseline BG values for insulin glulisine (136.4 ± 15.7 mg/dL; mean ± SD) and aspart (133.4 ± 14.7 mg/dL) were similar (P = .34). Mean increase in 2-hour postprandial BG was higher in glulisine (+113.5 ± 65.2 mg/dL) than aspart (+98.6 ± 66.9 mg/dL), (P = .01). BG remained higher at 4 hours (glulisine: 141.9 ± 36.5 mg/dL, aspart: 129.0 ± 37.0 mg/dL) (P = .04). Although statistically insignificant, more hypoglycemic events occurred at 2- and 4-hours postprandial with insulin aspart. CONCLUSION: Insulin aspart appears to be more effective than insulin glulisine in controlling 2- and 4-hour postprandial BG excursions in prepubertal children with T1DM.

Mosaic pentasomy X/tetrasomy X syndrome and premature ovarian failure.

A 16 year-old girl with pentasomy X mosaicism (47,XXX(1) 48,XXXX(12)/49,XXXXX) presented with primary amenorrhea. She had epicanthal folds, long philtrum, high-arched palate, facial asymmetry, short webbed neck, low posterior hairline, mild scoliosis, cubitus valgus, mental retardation and clinodactily. She was diagnosed with osteoporosis and premature ovarian failure.

Reliability of early iodine 123 uptake for treatment of Graves disease in children.

OBJECTIVE: To determine the reliability of early radioiodine uptake (RAIU) in calculation of the radioiodine ablation dose for pediatric patients with Graves disease. METHODS: This retrospective review of medical records involved 22 pediatric patients with Graves disease, who had undergone early (4 to 8 hours) and late (24 to 26 hours) RAIU studies and were treated with iodine 131 (131I). Quantitative data are reported as mean ± standard error of the mean. Early and late RAIU and actual administered versus calculated 131I ablation doses were compared by using the paired t test. The correlation between early and late RAIU was assessed by curvilinear regression analysis. Significance was assessed at P<.05. RESULTS: Mean early RAIU was 57.1% ± 18.2%, and mean late RAIU was 72.1% ± 14.4% (P<.05). Curvilinear regression analysis showed the following: late RAIU = 7.13 + 1.71 × (early RAIU) - 0.01 x (early RAIU)2; r2 = 0.75. The mean ablation dose of 131I based on late RAIU was 9.3 ± 2.0 mCi. The calculated radioiodine dose would have been, on average, 32% higher (12.3 ± 3.8 mCi; P<.05) had early RAIU been used. CONCLUSION: In children, early RAIU can be much lower than late RAIU. This may be misleading for ablation dose calculations. Therefore, late RAIU should be used to avoid overtreatment in children with Graves disease.

Comparison of low-dose and high-dose cosyntropin stimulation testing in children.

BACKGROUND: There is no consensus among pediatric endocrinologists in using low-dose (LD) versus high-dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic-pituitary-adrenal axis (HPAA) and suggests a new peak cortisol cut-off value for LD stimulation testing to avoid false positivity. METHODS: Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic-pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic-pituitary axis, n= 17). RESULTS: In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut-off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut-off of 14 µg/dL eliminated false positive results. CONCLUSIONS: LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long-term treatment. Using a lower cut-off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA.

Use of a real-time continuous glucose monitoring system in children and young adults on insulin pump therapy: patients' and caregivers' perception of benefit.

BACKGROUND: Real-time continuous glucose monitoring systems (RT-CGMS) are a recently introduced technology for type 1 diabetes and experience in children is limited. OBJECTIVE: To assess patient and caregiver's perception of benefits and disadvantages of RT-CGMS in children or young adults with type 1 diabetes mellitus (DM) on insulin pump therapy. SUBJECTS AND METHODS: Forty-three subjects (3-25 yr) on insulin pump therapy were included in the study. Thirty-four used RT-CGMS for a short-term trial (4 wk, ST group) and nine as a long-term tool (2-18 months, LT group). Forty subjects or their caregivers completed a questionnaire. RESULTS: On the basis of the questionnaire responses, hypoglycemia prevention was the most common perceived benefit (88%), followed by elimination of hypoglycemia-related anxiety (83%), ease of pattern management (85%), improvement of diabetes control (80%), improvement of quality of life (78%), and ease of diabetes care (78%). Negative effects included irritation/annoyance from the sensor alarm (48%) and insertion site bruising, pain, or irritation (43%). A small percentage of patients who were interested in purchasing the device (12%) decided against using it LT after a 4-wk trial on RT-CGMS. CONCLUSIONS: The most common perceived benefits of RT-CGMS are prevention of hypoglycemia and decrease in hypoglycemia-related anxiety. Negative effects are uncommon and seem to be unlikely to affect the decision to use RT-CGMS for a LT. A ST trial seems to be a valuable tool for the patient/caregiver in determining whether to purchase the device and in setting realistic expectations of its potential benefits.

Etiology of failure to thrive in infants and toddlers referred to a pediatric endocrinology outpatient clinic.

The aim of this study is to determine the underlying etiology of failure to thrive (FTT) in infants and toddlers referred to an outpatient pediatric endocrinology clinic. A chart review was done on FTT referrals to a pediatric endocrinology outpatient clinic between 2002 and 2005. Majority of patients (51.5%) had a purely nutritional deficiency. The endocrine etiologies included short stature due to being small for gestational age, constitutional or familial short stature (28.9%). The third most common etiology was gastrointestinal disease. Endocrine causes of FTT seem to be rare even in the selected population of patients referred to pediatric endocrine outpatient clinics. In the primary care setting, nutritional assessment and consultation seem to be adequate in the majority of cases. Only a small percentage of the patients with FTT will require a multidisciplinary approach and more extensive work-up.